Module 5: Clinical Outcomes by Disease Site - Tumor Control and Retreatment with Proton Therapy

The Abramson Cancer Center of the University of Pennsylvania

Tumor Control with Proton Therapy

As more patients are treated with proton therapy, long term results on various sites of disease will be reported. When the same dose and fractionation regimens are used for X-rays and protons, there are similar cure rates. It is clear continued research is necessary to establish the optimum doses and fractionation of treatment for specific tumors using protons. Because protons can significantly reduce the side effects of treatment as noted above, studies on escalation of dose are ongoing. For many sites, increasing the dose of radiation therapy to the tumor may increase the ultimate cure rates. There are enormous opportunities for the combination of proton therapy with chemotherapy and radiation sensitizers. This, in fact, may be where the largest benefit for proton therapy may be seen with integration in the overall treatment plan. There are
currently significant limitations on the ability to combine conventional radiation therapy with chemotherapy due to toxicity. Proton therapy, by reducing the amount of normal tissue exposed to radiation, offers great promise for a number of diseases to be treated with combined modality therapy which ultimately may be much more effective. Most proton centers are now offering clinical trials in a number of cancers to explore this benefit. Unfortunately, some patients experience a local recurrence of their cancer after treatment with radiation therapy. Only a minority of patients are curable after a recurrence because the normal tissues can not tolerate significant doses of additional radiation. Because protons can spare normal tissues, many patients that were not previously considered treatable again with X-rays may be treated with protons. This may further increase
the cure rates in some specific malignancies.

Any site treated in the body with standard X-rays is a reasonable target for proton therapy. The physical characteristics of the proton beam will allow markedly decreased dose to normal structures. Not only can malignancies be treated, but also there is currently significant interest in the treatment of a number of benign diseases. This includes functionally abnormal areas that can be safely ablated by protons for diseases such as seizures, Parkinson's Disease, arteriovenous malformations, macular degeneration, and severe rheumatologic conditions. There is also interest in evaluating protons for the prevention of coronary artery restenosis after angioplasty and prevention of stenosis of peripheral vascular shunts that are created in patients requiring dialysis. This will require ongoing investigation in clinical trials.

There are some preliminary data available on the treatment of macular degeneration. This is the leading cause of adult onset blindness in the United States. It is caused by the growth of blood vessels in the back of the eye, which are fragile and bleed. Current treatments include laser ablation, photodynamic therapy, standard X-ray therapy, and anti-angiogenic agents. Unfortunately, none of these treatments have been extraordinarily successful for most patients. Proton therapy offers the opportunity to safely deliver a much higher dose of radiation in a single treatment to the vessels in the back of the eye then is possible with standard X-rays. There are very encouraging preliminary studies from Loma Linda University Medical Center where over 200 patients have been treated with a single fraction of 14 Gy. The lesion control is 95% with either improvement in
vision or no worsening of vision. Side effects are very mild and seen in <10% of patients.